Mutation-Driven Immune Microenvironments in Non-Small Cell Lung Cancer: Unrevealing Patterns through Cluster Analysis.
Youngtaek Kim, Joon Yeon Hwang, Kwangmin Na, Dong Kwon Kim, Seul Lee, Seong-San Kang, Sujeong Baek, Seung Min Yang, Mi Hyun Kim, Heekyung Han, Seong Su Jeong, Chai Young Lee, Yu Jin Han, Jie-Ohn Sohn, Sang-Kyu Ye, Kyoung-Ho Pyo
Author Information
Youngtaek Kim: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Joon Yeon Hwang: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Kwangmin Na: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Dong Kwon Kim: Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Seul Lee: Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Seong-San Kang: JEUK Institute for Cancer Research, JEUK Co., Ltd., Gumi, Korea. ORCID
Sujeong Baek: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Seung Min Yang: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Mi Hyun Kim: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Heekyung Han: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Seong Su Jeong: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Chai Young Lee: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Yu Jin Han: Department of Research Support, Yonsei Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
Jie-Ohn Sohn: Wide River Institute of Immunology, Seoul National University, Hongcheon, Korea. ORCID
Sang-Kyu Ye: Wide River Institute of Immunology, Seoul National University, Hongcheon, Korea. ORCID
Kyoung-Ho Pyo: Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. ORCID
PURPOSE: We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data. MATERIALS AND METHODS: The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in , , , , , and the wild-type. RESULTS: Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: , , and + mutations (MC1); and , , and mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of , , and chemokines linked to alternative immune pathways. Remarkably, co-occurring and mutations were grouped as MC1. + mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to mutations. In T/NK cells, + mutations showed a higher expression of features related to cell activity and differentiation, whereas mutations showed the opposite. CONCLUSION: Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment.
